Circulating Proneurotensin Levels Predict Impaired Bone Mineralisation in Postmenopausal Women With Type 2 Diabetes Mellitus.

Context: The mechanisms underlying bone fragility and increased fracture risk observed in individuals with type 2 diabetes (T2D) are not yet fully elucidated. Previous research has suggested a role for neuropeptides in regulating bone metabolism; however, the contribution of the neuropeptide Neurotensin (NT), which is thoroughly implicated in T2D and cardiovascular disease, has not been investigated in this context.

Objective: To study the relationship between circulating levels of the NT precursor proneurotensin (proNT) and bone mineralisation in T2D women.

Materials And Methods: This is a cross-sectional investigation with a longitudinal prospective phase, involving 126 women with T2D who underwent bone density scans and had proNT levels measured. Biomarkers of bone metabolism and inflammation were also assessed. Data on bone mineral density (BMD) after 12 months were available for 49 patients.

Main Outcome Measure: Plasma proNT levels in relation to BMD.

Results: 32% of the participants had osteopenia/osteoporosis and exhibited higher proNT than those with normal BMD (200.8 ± 113.7 vs. 161.6 ± 108.8 pg/mL; p = 0.013). ProNT inversely correlated with femur BMD and T-score (p < 0.01) and was associated with degraded bone architecture (TBS, p = 0.02), and higher OPN, P1NP, TNF-α and IL-1β levels. Baseline proNT correlated with further BMD reduction at the 12-month follow-up, independently of potential confounders (p = 0.02).

Conclusions: In women with T2D, greater proNT levels are associated with impaired bone mineralisation and predict mineral density decline overtime. ProNT could potentially serve as a diagnostic tool for identifying patients at higher risk of osteopenia/osteoporosis, suggesting a significant connection between this neuropeptide and bone metabolism in diabetes.